It is proposed to study the overall structure and subunit topography of the oligomeric enzyme RNA polymerase from E. coli and to map its binding sites for templates, substrates, products and effectors. At present, very little is known about the structure of this enzyme. This is mainly due to the present lack of crystals suitable for single crystal X-ray diffraction analysis and the difficulty to reveal distinct structural features from electron micrographs of individual molecules. I have come to the conclusion that the most promising (and novel) approach to solving this problem is a combination of high resolution electron microscopy (CTEM and STEM) and analog and digital image processing technique applied to ordered aggregates of native and specifically labeled enzyme. Specific labels will include subunit-, template-, substrate-, product- and effector- specific antibody fragments and heavy metal labeled derivatives of these components. My preliminary results indicate that several types of ordered aggregates of core and holoenzyme can be induced (e.g., linear polymers, helical and 2-dimensional ordered arrays); some of them seem to be favored in the presence of bound template (e.g., oligonucleotides). Knowledge of the overall shape and the location and topography of the subunits and functional sites of the enzyme will contribute to a better understanding of its functions and regulation. Furthermore these structural data could be very helpful in the elucidation of the crystal structure, should suitable crystals ever become available.